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EP2369343B1 - Dispositif et procédé de manipulation ou d'analyse d'un échantillon liquide - Google Patents

Dispositif et procédé de manipulation ou d'analyse d'un échantillon liquide Download PDF

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Publication number
EP2369343B1
EP2369343B1 EP20100002685 EP10002685A EP2369343B1 EP 2369343 B1 EP2369343 B1 EP 2369343B1 EP 20100002685 EP20100002685 EP 20100002685 EP 10002685 A EP10002685 A EP 10002685A EP 2369343 B1 EP2369343 B1 EP 2369343B1
Authority
EP
European Patent Office
Prior art keywords
channel
carrier
sample
detection
support
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
EP20100002685
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German (de)
English (en)
Other versions
EP2369343A1 (fr
Inventor
Tobias Rodenfels
Gert Blankenstein
Dirk Osterloh
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Boehringer Ingelheim International GmbH
Original Assignee
Boehringer Ingelheim International GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to EP20100002685 priority Critical patent/EP2369343B1/fr
Application filed by Boehringer Ingelheim International GmbH filed Critical Boehringer Ingelheim International GmbH
Priority to AT10002685T priority patent/ATE542136T1/de
Priority to EP11711029.6A priority patent/EP2548023B1/fr
Priority to US13/583,785 priority patent/US8919383B2/en
Priority to EP11710687A priority patent/EP2547449A1/fr
Priority to JP2012557437A priority patent/JP2013522014A/ja
Priority to PCT/EP2011/001242 priority patent/WO2011113563A1/fr
Priority to JP2012557439A priority patent/JP5551279B2/ja
Priority to PCT/EP2011/001254 priority patent/WO2011113569A1/fr
Priority to US13/583,788 priority patent/US20130156643A1/en
Publication of EP2369343A1 publication Critical patent/EP2369343A1/fr
Application granted granted Critical
Publication of EP2369343B1 publication Critical patent/EP2369343B1/fr
Active legal-status Critical Current
Anticipated expiration legal-status Critical

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16K—VALVES; TAPS; COCKS; ACTUATING-FLOATS; DEVICES FOR VENTING OR AERATING
    • F16K99/00—Subject matter not provided for in other groups of this subclass
    • F16K99/0001—Microvalves
    • F16K99/0003—Constructional types of microvalves; Details of the cutting-off member
    • F16K99/0017—Capillary or surface tension valves, e.g. using electro-wetting or electro-capillarity effects
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502769—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/5302—Apparatus specially adapted for immunological test procedures
    • G01N33/5304—Reaction vessels, e.g. agglutination plates
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
    • G01N33/54326—Magnetic particles
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366—Apparatus specially adapted for solid-phase testing
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0647—Handling flowable solids, e.g. microscopic beads, cells, particles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0636—Integrated biosensor, microarrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/043—Moving fluids with specific forces or mechanical means specific forces magnetic forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0688—Valves, specific forms thereof surface tension valves, capillary stop, capillary break
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T137/00—Fluid handling
    • Y10T137/206—Flow affected by fluid contact, energy field or coanda effect [e.g., pure fluid device or system]
    • Y10T137/218—Means to regulate or vary operation of device
    • Y10T137/2202—By movable element
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T137/00—Fluid handling
    • Y10T137/206—Flow affected by fluid contact, energy field or coanda effect [e.g., pure fluid device or system]
    • Y10T137/218—Means to regulate or vary operation of device
    • Y10T137/2202—By movable element
    • Y10T137/2218—Means [e.g., valve] in control input
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T137/00—Fluid handling
    • Y10T137/206—Flow affected by fluid contact, energy field or coanda effect [e.g., pure fluid device or system]
    • Y10T137/2224—Structure of body of device

Definitions

  • the present invention relates to a device for manipulating and / or examining a liquid sample according to the preamble of claim 1.
  • the present invention is concerned in particular with the diagnostics of microfluidic samples, particularly preferably so-called point-off-care systems (POC systems).
  • the present invention is concerned with preferably miniaturized immunoassays, that is the study of samples using antibodies.
  • the present invention particularly preferably relates to so-called cartridge concepts, ie small, in particular card-type, devices for the manipulation and / or examination of a liquid sample or realization of immunoassays.
  • the US 2009/0227044 A1 discloses a device with a microchannel in which magnetic, luminescent nanoparticles serve as carriers for antibodies and as an internal luminescence standard.
  • the carriers are vibrated by an external magnetic field generated by electromagnets to achieve better diffusion during an incubation step. Further, the electromagnets are used to hold the particles in the channel for wash and luminescence measurements.
  • the WO 99/49319 A1 discloses a microsystem for manipulating magnetic particles.
  • the particles are coated with a reagent or antibody and moved by magnetic forces in the microfluidic system. Different particles can be provided with different reagents.
  • the evaluation is carried out magnetically and / or by fluorescence measurement.
  • the US 2002/0064866 A1 discloses fibrous spherical particles as carriers of substances for carrying out tests. For this purpose, substances are bound to the fissured surface of the particles or in their surface stored. The particles are grown as a suspension and held on demand by magnetic forces.
  • the US Pat. No. 7,105,357 B1 discloses a method with a pipette for generating minute droplets, wherein substances are bound to magnetic particles and these are held in the pipette by means of permanent magnets.
  • the US 5,135,720 A discloses a reaction vessel with a spherical support having a magnetic core and a coating on which proteins or peptides can be attached.
  • the carrier is levitated by electromagnets and a regulating mechanism to improve the efficiency of an Edman reaction with substances on the surface of the carrier.
  • the US 5,439,650 A discloses a similar device wherein a portion of the reaction vessel is slidable with the floating support and the electromagnet associated therewith.
  • the WO 2007/089564 A2 relates to a microchannel for examining samples.
  • the channel has external electromagnets and inside the channel magnetic or luminescent nanoparticles as a carrier for antibodies.
  • a manipulating device allows the carriers to move out of the sample.
  • a microfluidic system In the DE 10 2004 062 534 A1 a microfluidic system is described.
  • the system has particle fractions with fixed biomolecules that are guided serially and directionally through channels.
  • a magnetic field can be applied.
  • Karle et al. ( Karle, M; Miwa, Junichi; Roth, Günter; Haeberle, Stefan; Zengerle, Roland; von Stetten, Felix: “Continuously working microfluidic plate Form for purifying biomolecules "VDE Verlag GmbH, PAPER 31, 12 October 2009 (2009-10-12), pages 1 to 4, XP002590553 Berlin Offenbach ISBN: 978-3-8007-3183-1 ) relates to a microfluidic platform for the purification of biomolecules.
  • the platform has channels and a rotatable permanent magnet acting on the platform. Magnetic beads moving in small filaments along magnetic lines transport biomolecules to be purified through the channels.
  • a separation chamber receives purified DNA with beads, with the liquid being eluted through an outlet.
  • the plurality of small magnetic, substantially spherical or other undefined shape particles does not allow optimal manipulation or examination of a liquid sample.
  • no optimal optical detection of the binding of analytes or complexes to the carrier particles is possible.
  • the object of the present invention is to provide a device and a method for manipulating and / or examining a liquid sample, in particular in a microfluidic system or channel, wherein optimized manipulation or examination and / or improved, preferably optical detection - in particular for Proof of a reaction or for the determination of an analyte - is or will be made possible and / or wherein several examinations can be performed in parallel on a sample under defined conditions and / or spatially separated.
  • microfluidic is to be understood as meaning volumes of preferably less than 10 ml, more preferably less than 1 ml, and / or channel or liquid cross-sections (maximum diameter) of preferably less than 2 mm, particularly preferably less than 500 ⁇ m ,
  • a carrier which is movable in a preferably microfluidic channel or system and has at least one detection or binding region for a substance is used.
  • This may be an analyte of the sample or a complex formed therefrom or its dependent reaction product and / or a reagent that interacts or binds with the sample, an analyte of the sample, a complex thereof or the like.
  • the reagent may interact or bind with a complex of the analyte or with an analyte-dependent reaction product.
  • the reagent itself is fixed or immobilized in or on the detection or binding region.
  • the detection or binding region may contain or have an immobilized antibody which interacts with an analyte of the sample or a complex containing the analyte, particularly preferably binds.
  • the reagent is formed by the antibody, which interacts indirectly with the analyte, namely with a complex containing the analyte or the like.
  • the term "interacting" is preferably to be understood in a broad sense in the present invention.
  • the carrier is at least substantially flat or plate-shaped and / or in particular provided with an at least substantially flat or flat upper side with the detection or binding region. This is conducive to good or defined detection or determination of an analyte.
  • the carrier is guided in a defined orientation in or from the channel.
  • the carrier is not reversible in the channel, but preferably has a flat side and / or its side containing the detection or binding area to a side (in particular flat side) of the device or of the channel. This allows a particularly good, in particular optical detection of the latter side and thus simplifies the structure of the device or the detection in general.
  • the carrier has a length that is greater than the maximum cross-section of the channel. This allows a much more defined movement and / or orientation of the carrier in the channel or microfluidic system than in the prior art. Thus, a much more defined process flow and / or a better or more defined, in particular optical detection can take place.
  • the carrier fills the cross-section of the channel to more than 30%, preferably more than 40%, in particular more than 50% in terms of area.
  • the carrier is formed dimensionally stable with a defined shape. This in turn is conducive to defined detection.
  • only a single carrier is provided for detection and / or in the channel. This is conducive to defined detection.
  • the carrier in particular by means of a manipulation device, is movable out of the sample, in particular in a gas space, or over or through a phase boundary. This in turn is conducive to a particular optical detection.
  • detection in the present invention is preferably understood to mean the detection of an interaction, modification or reaction in the detection or binding region and / or the binding of a substance, such as an analyte, complex or the like, in the detection or binding region in order to allow a preferably qualitative and / or quantitative examination of the sample, in particular a qualitative and / or quantitative determination of at least one analyte of the sample.
  • the detection can be carried out in particular optically, particularly preferably by luminescence or fluorescence measurement.
  • the carrier is designed as a plastic part and / or injection molded part. This allows a simple, cost-effective production and / or the realization of defined properties and / or a facilitation of mass production.
  • the detection or binding region is at least partially microstructured.
  • microstructuring is preferably a particularly repeating structure and / or a structure having an average structure width of 10 nm to 500 .mu.m, preferably less than 10 .mu.m, and / or with elevations or depressions of 10 nm to 500 .mu.m, preferably less than 10 ⁇ m, to understand.
  • the microstructuring serves to increase the surface area and / or facilitates the binding of a substance, such as an analyte or reagent, in particular an antibody or the like, in the detection or binding region.
  • the carrier may be movable into different liquids, for example from the liquid sample to another liquid or vice versa, and / or optionally into different reaction chambers. This in turn is conducive to an optimized reaction procedure, an optimized sequence of different steps and / or an optimized detection.
  • the carrier is moved out of the sample into a gas space of the system for detecting a substance bound in the detection or binding region.
  • This allows an optimized, in particular optical detection, particularly preferably by means of luminescence or fluorescence measurement.
  • the support 4 can be moved through the gas space, into a liquid other than the sample, or vice versa.
  • steps such as incubation steps, washing steps or the like, in particular with minimal liquid volumes can be realized.
  • Fig. 1 shows a schematic plan view of a device according to the present invention 1 for manipulating or examining a liquid sample 2.
  • the device 1 is preferably at least substantially card-like, plate-like, flat, thin and / or flat.
  • the device 1 preferably has (at least) one in particular microfluidic channel 3 for receiving the sample 2.
  • the channel 3 or the device 1 forms in particular a microfluidic system or a part thereof.
  • the device 1 preferably comprises a base part 1A, in which the channel 3 or the microfluidic system in particular by one or more depressions - preferably in the form of a groove or a plurality of grooves - is or are covered by a cover 1B is or are.
  • the base part 1A is preferably formed as a plastic part and / or injection molded part.
  • the base part 1A is preferably at least substantially flat, flat, plate-like and / or rigid.
  • the channel 3 or the microfluidic system is preferably formed in or along a flat side of the base part 1A and / or open to a flat side.
  • the channel 3 or the recess or flat side is preferably at least substantially completely covered by the cover 1B.
  • other constructive solutions are also possible.
  • the lid 1B is preferably formed as a film.
  • the lid 1B is preferably glued or laminated and / or welded.
  • the lid 1B is formed by an adhesive sheet or heat-sealing foil or the like.
  • the cover 1B is preferably designed to be transparent, at least in some areas, in particular in order to enable optical detection, as described in more detail below.
  • the device 1 has at least one carrier 4 movable in the channel 3 or system and / or in the sample 2.
  • the carrier 4 is preferably movable into the sample 2 and / or movable within the sample 2 as indicated by the dashed position A in FIG Fig. 1 in particular, in order to enable an examination or interaction with the sample 2 or components of the sample 2, such as an analyte.
  • the carrier 4 is out of the sample 2 - in the representation example according to Fig. 1 into another area of the channel 3 or system - movable, as indicated by position B,
  • the carrier 4 preferably has at least one detection or binding region 5, in the representation example two or more detection or binding regions 5.
  • the function of the detection or binding region 5 or the detection or binding regions 5 will be explained in more detail below, with particular reference to FIGS Fig. 2 Reference is made, which shows the device 1 in a schematic longitudinal section in position B.
  • Each detection or binding region 5 preferably interacts only with one substance.
  • the substance is preferably an analyte of sample 2 or a product derived therefrom or dependent, such as a complex or a complex, or a reagent that interacts or binds with the analyte or product dependent thereon.
  • a detection or binding region 5 serves to bind a specific substance, such as a component or analyte of the sample 2 and / or a complex 6 formed therefrom, and / or the binding of a reagent to the sample 2 or a component or Analyte of sample 2 or complex 6 formed therefrom interacts.
  • the reagent or substance according to the illustrative example is particularly preferably one or more, possibly also different, antibodies 7 which interact or bind with an analyte or a complex 6 or other product of the analyte.
  • the detection or binding region 5 is formed or covered by immobilized antibodies 7.
  • detection region in the present invention is preferably understood to be very general in that it interacts directly or indirectly (e.g., after pretreatment or application of antibodies 7) with the substance, particularly an analyte.
  • the interaction may be a reaction, a binding, a complex formation, an adhesion, an attachment, a catalytic effect or any combination thereof.
  • the support 4 preferably has a plurality of detection or binding regions 5, which are spatially separated from one another, which interact in particular with different substances or serve to determine different analytes of the sample 2, as indicated in the illustration example.
  • the proposed device 1 and the proposed method are therefore preferably used to examine or diagnose the sample 2, in particular the qualitative and / or quantitative determination of at least one analyte of the sample 2.
  • an immunoassay is realized, particularly preferably as a sandwich immunoassay.
  • other reactions may be run or other substances, reaction products, properties or the like may be determined or measured or detected.
  • the proposed device 1 and the proposed method for manipulating the sample 2 in particular by moving the carrier 4 within the sample 2 and / or by moving out of the carrier 4 from the sample 2 and / or Hineinbe admire the carrier 4 in the Sample 2 can be used.
  • a mixing of the sample 2 or a transfer of a certain amount of the sample 2 or a component of the sample 2 can be realized.
  • by moving the carrier 4, a transfer to the sample is possible.
  • the device 1 preferably has a manipulating device 8.
  • the manipulation device 8 may be the device 1 but also be assigned, in particular form part of a test device, as explained later.
  • the movement of the carrier 4 takes place in the illustrated embodiment, preferably magnetically, in particular by varying a force acting on the carrier 4 magnetic field M.
  • the magnetic field M is generated externally.
  • the manipulation device 8 for this purpose has at least one external magnet and / or electromagnet or a plurality of electromagnets, as in FIG Fig. 2 implied
  • the carrier 4 is at least partially made of magnetic or magnetizable material or provided therewith, which in particular forms a magnet 9, as in Fig. 2 In particular, this is a paramagnetic, superparamagnetic or ferromagnetic material.
  • the magnetic material or the magnet 9 can be accommodated, for example, in the carrier 4, as in FIG Fig. 2 indicated, or glued or attached thereto or glued or, for example, be poured into it.
  • the carrier 4 may also be made at least substantially of magnetic or magnetizable material. If necessary, several or different magnetic materials or magnets 9 on the support 4 - for example, spatially distributed or spaced from each other - are attached or used, in particular to achieve a certain controllability or mobility of the support 4.
  • the carrier 4 is movable further along a gradient of the magnetic field M acting on the carrier 4, ie in particular of the magnetic field M generated by the manipulating device 8, in particular in a region of high magnetic field strength ,
  • the carrier 4 By correspondingly changing the magnetic field M or the gradient of the magnetic field M, the carrier 4 can be moved in a specific direction, in a specific region and / or in opposite directions. By correspondingly rapid changes, in particular change of direction the gradient of the magnetic field M, an optionally very fast reciprocating motion or alternating movement of the carrier 4 or, a swinging of the carrier 4 can be realized.
  • the support 4 can also be in any other manner, for example by the action of gravity, for example when panning or turning over, or by the action of another force or acceleration, for example during rotation of the device 1, by electrical attraction or repulsion friction or form liquid attack on the carrier 4, for example by means of a thread or other traction means or pressure medium, carried out by ultrasound or the like.
  • the carrier 4 is preferably movable in the longitudinal direction or along the channel 3 at least in one direction or in both directions.
  • the carrier 4 optionally has at least one guide means 10 in that in the illustrated example, in particular a plurality of projections or runners is formed.
  • the guide means 10 or the projections or skids facilitate the sliding of the carrier 4 on the base part 1A and the bottom of the channel 3, in particular reduce the sliding resistance, and / or, if necessary, engage in a not shown groove or longitudinal groove or the like
  • the guide means 10 may alternatively or additionally also be spaced from the base 4 of the channel 3, to side walls of the channel 3 and / or to the carrier 4, or in the longitudinal direction of the channel 3 Guide or hold lid 1B and / or spaced from the bottom of the channel 3, to side walls of the channel 3 and / or to hold the lid 1B.
  • the carrier 4 is preferably guided in a defined orientation in the channel 3 or by means of the channel 3. This facilitates the detection.
  • the carrier 4 is formed at least substantially flat or plate-like and / or preferably has one at least substantially level top with the detection or binding region 5 and the detection or binding regions 5 on. This facilitates in particular the detection.
  • the carrier 4 has a length that is greater than the maximum cross section of the channel 3. Accordingly, the carrier 4 is guided through the channel 3 at least in the longitudinal direction.
  • the channel 3 is formed at least substantially flat or flattened in cross-section, in particular so that the carrier 4 is not reversible in the channel 3, in particular due to the opposite the relatively small clear height of the channel 3 has a comparatively greater width.
  • the support 4 fills the cross-section of the channel 3 more than 30% in terms of area, in particular to more than 40% or 50%, as shown schematically in the cross-section according to FIG Fig. 3 indicated.
  • the detection is facilitated Furthermore, thereby the fusion lengths can be reduced and / or required sample volumes are minimized.
  • the carrier 4 is preferably formed dimensionally stable with a defined shape. This in turn is conducive to defined detection.
  • the carrier 4 or at least its surface with the region 5 or the regions 5 is made of or coated with a non-luminous and / or non-fluorescent material. This facilitates the detection of substances connected in area 5.
  • the carrier 4 or its surface with the at least one region 5 is at least substantially dark or particularly preferably black. This is conducive to optical detection.
  • the carrier 4 is preferably formed very thin. In particular, its thickness (without guide means 10) is substantially between 10 ⁇ m and 500 ⁇ m.
  • the length and / or extent in the movement device V of the carrier 4 is preferably between 1 mm and 10 mm.
  • the width of the Carrier 4 is preferably between 0.5 mm and 5 mm.
  • the length of the carrier 4 corresponds to its main extension.
  • the width of the carrier 4 is at least a factor of 2, in particular by a factor of 3 or more greater than its thickness.
  • the length of the carrier 4 preferably corresponds at least to the 1.5-flat, in particular at least 2-times or more, the width of the carrier 4.
  • the longitudinal extent of the channel 3 is preferably at least twice the length of the carrier 4, in particular between 10 and 100 mm.
  • the channel 3 preferably has at least substantially a rectangular cross-section or forms such.
  • the clear height of the channel preferably corresponds at least to the thickness of the carrier 4 or, in particular at least 10%, more than this thickness, in particular between 10 .mu.m and 1 mm.
  • the clear width of the channel 3 corresponds at least to the width of the carrier 4, in particular at least 10%, more. In particular, the clear width of the channel can be between 0.5 and 10 mm.
  • the carrier 4 is preferably at least substantially in its main extension plane - in particular in the channel 3 and in the system - movable.
  • the relatively thin design of the carrier 3 is beneficial to a low flow resistance.
  • the carrier 4 is preferably at least substantially linearly movable in the channel 3 and / or in the channel 3 back and forth.
  • the channel 3 is not rectilinear, but for example, winding or meandering or otherwise runs or is bent.
  • the carrier 4 may then preferably be moved according to the channel 3 or in a portion or region of the channel 3.
  • a single movable support 4 is provided in the device 1 or the channel 3 or the system. This is conducive to a defined movement and / or detection.
  • the carrier 3 is preferably made of plastic or, a plastic part. This allows a favorable production or the use of material with desired properties.
  • the carrier 4 is at least substantially made of PMA or PE.
  • the carrier 3 is preferably an injection molded part or produced by injection molding. This allows a simple and inexpensive production and / or shaping.
  • At least the upper side or flat side of the carrier 4 with the at least one detection or binding region 5 is at least essentially flat or smooth.
  • the upper side or the detection or binding region 5 can also be microstructured or structured in any other way as required be.
  • the structuring is, for example, in the schematic section according to Fig. 2 indicated in the areas 5.
  • microstructuring can facilitate the binding of reagents such as antibody 7.
  • the binding of the antibodies 7 or other reagents is particularly preferred is a plasma treatment of the carrier 4 or its top or flat side and / or the regions 5 and particularly preferably immobilization of the antibodies 7 on the carrier 4 or in the regions 5 he follows.
  • the carrier 4 is preferably movable into different regions of the channel 3 or microfluidic system and / or into different liquids. This will be explained in more detail below.
  • the carrier 4 is initially preferably movable within the sample 2 in the illustrated example, for example, reciprocating or alternating and / or vibratable thereto.
  • the region a of the channel 3 or the system in which the sample 2 is located preferably forms a reaction chamber.
  • the sample 2 is located only in this channel region a, so it is limited to a part of the channel 3.
  • the channel 3 or the system preferably has a region b, which forms a gas space, that is not filled with the sample 2 or other liquids.
  • the carrier 4 is preferably in the area from the area a b, that is, from position A to position B, movable and / or vice versa, preferably by means of the manipulation device 8.
  • the carrier 4 is movable out of the liquid sample 2 or into it or over a phase boundary liquid-gas or gas-liquid 11 , in the Fig. 2 is indicated.
  • the carrier 4 is movable out of the sample 2 or out of the reaction chamber into the gas space or vice versa.
  • the detection is particularly preferably carried out in the gas space or outside a liquid. This is particularly beneficial for optical detection.
  • a means 12 is preferably provided to retain liquid.
  • the means 12 is a capillary stop or an abrupt cross-sectional widening, for example by a trench 13 formed in particular both in the bottom and in sidewalls of the channel 3.
  • the means 12 may additionally also be provided by a surface area with different surface properties may be formed, for example, hydrophobic, if the retained sample 2 or other liquid is hydrophilic, or vice versa.
  • the means 12 serves a "stripping" of the liquid or sample 2 from the carrier 4 when it is out of the liquid or sample 2 out - in particular directly into a gas space and / or a phase boundary 11 - moves.
  • the means 12 can, in particular for this stripping, successively have a plurality of regions with reduced capillarity or different surface properties, for example a plurality of grooves, grooves 14 or the like, which are preferably smaller than the trench 13 in the illustrated embodiment.
  • other constructive solutions are possible here.
  • the means 12 is preferably arranged between the region a and b or in the region of the transition from the region a or sample 2 to the region b or the gas space.
  • the trench 13 is arranged with the significantly reduced capillarity or the capillary directly directly adjacent to the reaction chamber or the area b or to the sample 2, wherein the further means for stripping liquid or grooves 14 or the like then preferably that of the liquid or sample 2 opposite Side - so the gas space - to the trench 13 or the like connect.
  • the carrier 4 is preferably movable in different positions.
  • the carrier 4 can be brought into contact with various liquids.
  • a change of the liquid is carried out according to the proposal preferably a corresponding movement of the carrier 4 and a change in the position of the carrier 4.
  • the liquid 15 is preferably received or held in a region c of the channel 3 or microfluidic system or the device 1.
  • the region c preferably forms a further reaction chamber.
  • the support 4 is preferably movable starting from the position a or from the sample 2, in particular over the region b or the gas space into the further liquid 15 or reaction chamber and / or the region c, as shown by position C in FIG Fig. 1 indicated.
  • the carrier 4 is thus movable, for example, from the position A via the position B in the position C.
  • the carrier 4 can in principle also be oppositely movable.
  • a means 12 for retaining the liquid 15 is again preferably provided, as in FIG Fig. 1 indicated.
  • the region b or the gas space is arranged between the region a or the reaction chamber formed therefrom and / or the sample 2 on the one hand and the region c or the reaction chamber formed therefrom and / or the liquid 15 on the other hand.
  • the gas space or region b arranged therebetween can also be omitted or greatly shortened, for example, be formed only by a means 12 or only by a larger trench 13 or the like.
  • the gas space or the means 12 between the areas a and c can be shortened in such a way be that the area b quasi deleted and / or shorter than the length of the carrier 4 is.
  • the means 12 or the grooves 14 or the like extend over a distance in the direction of movement of the carrier 4 or longitudinal extent of the channel 3, which corresponds substantially to the length of the carrier 4 or in particular is significantly longer.
  • the means 12 between the sample 2 and liquid 15 or between two other liquids can be dispensed with altogether, in particular if the liquids are immiscible and form a phase boundary, for example by appropriate stratification, by which the carrier 4 is movable
  • the device 1 or the channel 3 or the system preferably or optionally on the liquid other than the sample 15, a further liquid 16, in which the carrier 4 (as needed) is movable.
  • the device 1 or the channel 3 or the system preferably has a further regions for receiving or for holding the liquid 16.
  • the carrier 4 is in the illustrated example, starting from the position C or from the region c over a region d, which forms an optional further gas space, or via the position D in the region e or the position E, ie in the further liquid 16 movable.
  • each region c and d on the one hand, and the regions d and e, on the other hand, preferably in each case means 12 or trenches 13 and / or grooves 14 or the like are arranged.
  • the means 12 of the device 1 or of the channel 3 can in principle be designed to be at least substantially the same or as required, for example due to the use of different liquids or the like, also differently.
  • the carrier A is preferably movable starting from the position A via the position B, C and D in the position E.
  • the residence time of the carrier 4 in the individual position or areas and / or in the individual liquids or in the sample 2 can be varied as desired.
  • the detection is particularly preferably carried out in a gas space.
  • a detection in the area b or d or in the position B or D done. Possibly. can also be carried out in both areas or positions in each case a detection, ie in Hereen different areas or positions a successful detection gene. If necessary, different detections can be made in the different areas or position.
  • multistage or different reactions can be carried out, detected or monitored in succession.
  • the carrier 4 is preferably moved into different reaction chambers. It can also be changed in a reaction chamber or in an area the respective liquid if necessary. For example, instead of the first liquid-forming sample 2 before or after another liquid can be filled in the area a. For or when changing the liquid, the carrier 4 can then either either remain in the region a or be moved to another region, in particular into the gas space or adjacent region b.
  • the individual areas may have a different length.
  • individual or all filled with liquid areas here the areas a, c and e, each adapted to the size or length of the carrier 4 such that the carrier 4 - if desired - in sufficient extent within the respective area or within the liquid is movable, but on the other hand, the required liquid volume is low or even minimized.
  • This can be done by adjusting the length of the respective area.
  • the length is particularly preferred the respective area and / or the longitudinal extent of the means 12 preferably at least substantially each between 1.2 times and 10 times, more preferably between 1.5 times and 3 times the length of the carrier 4 or extension of the Carrier 4 in the direction of movement.
  • the carrier 4 Due to the volume displacement by the carrier 4, it may be possible or expedient to dimension the required liquid volume so that in particular the preferred longitudinal extent or an at least substantially complete filling the respective areas (especially first) in the state of the present in the liquid carrier. 4 be achieved. This too can lead to a minimization of the liquid volume required in each case.
  • a minimization of the required liquid volumes can be achieved in that the carrier 4 fills the channel 3 in cross section in area to at least 30%, preferably more than 40%, in particular more than 50%.
  • the carrier 4 is formed in cross section at least substantially konkludent to the cross section of the channel 3 or vice versa.
  • the carrier 4 is preferably movable in the longitudinal extension of the channel 3 and along the channel 3, as by case V in Fig. 2 indicated schematically.
  • the support 4 can also be movable transversely thereto, in particular in its surface extension and / or parallel to the surface extension of the device 1 or the base part 1b or cover 1a, preferably by means of the manipulation device 8 and / or by other actions.
  • the manipulating device 8 preferably has a plurality of correspondingly positioned electromagnets, wherein the electromagnets in particular in required Are controllable in order to achieve the desired magnetic field M or the desired gradient.
  • the position of the carrier 4 in the device 1 or in the channel 3 or microfluidic system can be detected.
  • This is done in particular inductively.
  • this can be done inductively by means of a corresponding coil or a plurality of coils and / or by means of the electromagnets or the coils of the electromagnets of the manipulation device 8.
  • the detection of the position of the carrier 4 additionally or alternatively in other ways, for example, optically done.
  • the channel 3 preferably has an at least substantially constant cross-section and / or an at least substantially smooth or flat bottom or other guide surface for the carrier 4.
  • the means 12, trenches 13 and / or grooves 14 or the like are preferably relatively short interruptions and / or cross-sectional widenings in the direction of movement V of the carrier 4, ie they have a particularly short extent in this direction, in particular a good guidance of the carrier 4 and / or to allow easy movement or sliding of the carrier 4 or to make sure.
  • guide means may be formed, which are for example web-like, rail-like or runner-like and / or project to reduce the sliding resistance of the carrier 4 and / or to guide the carrier 4, for example, longitudinally displaceable.
  • the device 1 preferably has at least one detection device 17, which in particular comprises one or more measuring or sensor devices 18, as in FIG Fig. 2 indicated.
  • the detection device 17 may also be associated with the device 1, in particular forming part of a test device, as will be explained later.
  • the detection device 17 is in particular for the detection of an analyte or substance, such as a complex 6 of the analyte, optionally also of various substances or complexes 6 of different analytes, which are present at a region 5 or in different substances or regions 5 of the carrier 4, in particular bound, formed,
  • the detection device 17 preferably operates optically, in particular by a luminescence or fluorescence measurement. This is possible for example because the substances or complexes 6 or the analytes to be detected contain corresponding optical properties or markers. For example, by means of the detection device 17 or by means of corresponding measuring or sensor devices 18, it is also possible to determine a plurality of different or different substances or analytes, in particular in or on different regions 5, as in FIG Fig. 2 only indicated schematically.
  • the detection is therefore preferably optical, in particular by fluorescence or luminescence. However, additionally or alternatively, any other detection can take place.
  • the measured values of the detection device 17 can be evaluated and / or further processed in the detection device 17 and / or separately therefrom - in a separate evaluation unit, not shown - and in particular also displayed or output in any other way.
  • a separate evaluation unit not shown - and in particular also displayed or output in any other way.
  • the content of a particular analyte or the contents of various analytes in the sample 2 can be stored, displayed and / or output.
  • the proposed device 1 is particularly suitable or intended for the adaptation and implementation of miniaturized immunoassays.
  • the proposed device 1 is in particular a cartridge concept.
  • the proposed device 1 is in particular provided or suitable for measuring parameters or analytes in blood plasma, blood serum or the like as sample 2.
  • the device 1 preferably has a receptacle 19a for the sample 2 or blood or other body fluid or the like.
  • the receptacle 19a is formed for example as a receiving opening in the lid 1b, but can also be realized in other ways.
  • the receptacle 19a is connected, for example, via a connecting channel 2 to the channel 3 or its region a or the reaction chamber formed therefrom, in order to guide the sample 2 or the like in particular automatically by capillary forces into the reaction chamber or into the region a and with it to fill the sample 2.
  • the receptacle 19a or device 1 may additionally contain a device for separating blood, such as a filter, a membrane or the like, in particular the blood plasma or blood supplied for example in the receptacle 19a or blood supplied in another way Separate blood serum and pass as sample 2 in the area a or the reaction chamber formed thereof.
  • a device for separating blood such as a filter, a membrane or the like, in particular the blood plasma or blood supplied for example in the receptacle 19a or blood supplied in another way Separate blood serum and pass as sample 2 in the area a or the reaction chamber formed thereof.
  • the device 1 makes it possible to minimize the * sample and reagent requirements.
  • the proposed device 1 allows a simple structure, a simple design, a simple assembly and / or a simple handling.
  • the device 1 allows a miniaturized detection, in particular fluorometric detection.
  • the proposed device 1 allows the simultaneous detection or determination of several parameters or analytes.
  • the proposed device 1 forms a closed system, in particular self-contained.
  • other than the sample 2 or the blood or other liquids should or should be added no further reagents, substances or the like.
  • the device 1 particularly preferably allows the performance of classical, modified and / or miniaturized immunoassays, more preferably in the form of sandwich assays or competitive immunoassays.
  • a basic idea of the proposed device 1 method is to move a fat body, namely the carrier 4, through a cavity, in particular in the form of the channel 3, another chamber or in another, in particular microfluidic system.
  • the movement is effected in particular by a magnetic field gradient, as already explained.
  • the sample 2 e.g. pressure-driven and / or by capillary forces, transported or conducted in the reaction chamber or in the channel 3 or the region a.
  • the reaction chamber or the region a is preferably filled with a defined volume of the sample 2.
  • reaction chamber or the region a can simultaneously serve as a chamber for the reaction and detection.
  • the sample 2 is preferably brought into contact with a reagent 21, which is particularly preferably held in a dry form or is already in the channel 3 or area a or the reaction chamber.
  • a reagent 21 is particularly preferably held in a dry form or is already in the channel 3 or area a or the reaction chamber.
  • the reagent is disposed in the lid 1B and applied thereto and dried.
  • the reagent 21 is dissolved by the sample 2 and can react with the sample 2 or an analyte of the sample 2. If required, the dissolution of the reagent 21 can be assisted by a corresponding movement of the carrier 4 in the region a or in the reaction chamber.
  • the carrier 4 may already be located in the reaction chamber or the region a when the sample 2 is introduced or may only be moved into it after the sample 2 has been introduced therein.
  • the reagent 21 preferably contains a conjugate for an analyte of the sample 2 to be determined. If required, the reagent 21 can at least essentially only be determined from the conjugate and / or contain other substances and substances. Preferably, the reagent 21 or the conjugate has at least partially an especially fluorescent and / or luminescent and / or other marker property.
  • the reagent 21 or conjugate which is initially stored in dry form, is reconstructed with the sample 2. It may then react with the analyte in sample 2 and in particular form an analyte-conjugate complex 6.
  • analyzable surface 4A or, in the preferably visible detection or binding region 5 or in the preferably visible detection or binding regions 5 in the illustrated embodiment are particularly preferred catcher 7 or other complex with the 6th reacting substances preferably immobilized.
  • the mobility or mobility of the carrier 4, the geometric freedom in the design and arrangement of the regions 5 and / or by the controlled movement, in particular by means of a magnetic field M or magnetic field gradients result in many handling and functional possibilities.
  • the sample 2 and the conjugate for example, can be ideally homogenized and reacted. Furthermore, an optimal complex formation or other reaction can take place.
  • the carrier 4 can simultaneously assume the function of a mixer.
  • a sandwich complex can be formed.
  • the analyte-conjugate complex 6 reacts with the immobilized antibodies 7 on the support 4 and forms a sandwich complex (Capture antibody - analyte, detector antibody).
  • This condition is schematic in Fig. 2 in which case the carrier 4 has already been moved out of the sample 2 or out of the region A into another region, in particular into the region b or a gas space.
  • the conjugates may also be designated as detector antibodies or contain or be formed therefrom, in particular since they are intended to react or bind specifically with the analyte of sample 2.
  • the reagent 21 or conjugate preferably contain an optical marker or an optically active substance which, if appropriate, may also be formed by the detector antibody itself.
  • the washing liquid is introduced into the reaction chamber or the region a and thereby the sample 2 displaced or removed, for example via an overflow channel, not shown, in a Kochlaulhunt, not shown, or the like.
  • the carrier or its surface 4A or the region 5 is washed simultaneously.
  • the introduction of the washing liquid can be effected for example by compressed air and / or capillary force and / or in any other way.
  • the sample 2 can also be removed or removed beforehand, ie before the washing liquid is introduced.
  • the washing liquid is held or received in a separate reaction chamber or in a separate region c of the device 1.
  • the liquid 15 and / or 16 forms such a washing liquid or another, different from the sample 2 or different liquid.
  • the carrier 4 is then washed by moving into the liquid 15 and / or 16 or in the corresponding areas c and / or e, or subjected to other reactions or treatments.
  • the filling of the liquids 15 and 16 is preferably carried out via corresponding receptacles 19c and 19e and connecting channels 20c and 20e.
  • the filling can be done in particular in a similar manner as the filling of the device 1 with the sample 2, so that the relevant statements apply accordingly.
  • the receptacles 20c and 20e are preferably again formed by filling openings in the lid 1b.
  • the transfer of the liquids 15 or 16 into the corresponding regions c or e or thereof formed reaction chambers again takes place preferably by capillary forces, optionally by compressed air and / or in any other suitable manner.
  • the liquids 15 and 16 can basically be different liquids. However, it may also be the same liquid, for example a washing liquid. In this case, the two areas c and e or the reaction chambers formed therefrom may, if necessary, also be fillable with the liquid via a common receptacle.
  • the detection takes place.
  • the detection is carried out in particular optically, particularly preferably from the side to which the surface 4A or the region 5 has, on which is detected.
  • these are particularly preferably arranged on a common flat side, surface 4A or upper side of the carrier 4.
  • a fundamentally different arrangement is possible.
  • the carrier 4 separate or different areas 5 may be formed.
  • a detection can also take place from different sides and / or in different places.
  • the various regions 5 may be used simultaneously or sequentially for reactions or for binding analytes or the like and / or for detection.
  • a detection is basically possible either through the base part 1A or through the lid 1B.
  • the detection preferably takes place through the lid 1B.
  • the cover 1B is sufficiently transparent at least in the required detection area.
  • the carrier 4, with its region 5 or its regions 5, preferably points towards the lid 1B accordingly.
  • the carrier 4 or its detection or binding region 5 or several or all detection or binding regions 5 can be pressed against the preferably transparent wall.
  • a pressing against the lid 1A or vice versa is possible.
  • the cover 1A can be designed here to be, for example, elastically deformable, in particular a film-like manner. This allows in particular to reduce or minimize the influence of liquid on the optical detection when the carrier 4 is still in the liquid for detection or is still covered with (residues of) liquid. Also, disturbances due to transitions from and / or to the gas phase can be avoided. At the same time, this results in a particularly precise positioning and / or focusing of the surface for the optical measurement, in particular the preferred luminescence or fluorescence measurement.
  • the detection or the optical measurement takes place in a gas space, ie when the carrier 4 has previously been moved out of the respective liquid, such as the sample 2, liquid 14 or 16.
  • the respective liquid such as the sample 2, liquid 14 or 16.
  • the detection is preferably carried out optically or by measuring or determining the luminescence, preferably the photoluminescence, in particular the fluorescence.
  • the detection device 17 or its measuring or sensor device 18 is designed accordingly and includes, for example, a CCD sensor or other photosensor or the like.
  • the detection device 11 preferably also includes a corresponding light source or the like.
  • the detection which preferably takes place in a gas space, can take place, for example, in the region b and / or d.
  • a detection in liquid so in particular in the range a, c and / or e take place.
  • the carrier 4 may be provided with corresponding markings, optically detectable regions, in particular fluorescent regions or the like.
  • the detection or measured values can be evaluated in the detection device 11 itself and / or in a downstream evaluation and output in particular in the form of a content of the analyte to be detected in the sample 2. With different analytes to be detected, different contents or other different parameters can be output accordingly.
  • the pressing of the carrier 4 on the transparent wall or the cover 1B can also be done by the manipulation device 8 or magnetically.
  • the proposed device 1 is universally applicable and allows in particular the controlled flow of multi-stage reactions and / or the detection of various substances or analytes and / or a determination of various parameters.
  • the device 1 may also form part of a larger microfluidic system or drain.
  • the device 1, the channel 3 or the particular microfluidic system may have a plurality of, in particular two or more, carriers 4 which are optionally simultaneously or successively inserted into the sample 2 or the reaction chamber or region 2 and / or into a gas space or other reaction chamber or liquid 15 or 16 are movable.
  • the carriers 4 are then used in particular for the detection or determination of different analytes and / or parameters or the like.
  • the device 1 or the channel 3 is preferably provided with a suitable vent.
  • at least one ventilation duct 1 C is provided, which is connected in particular to a gas space.
  • a separate venting channel 1C is connected to a gas space, here to the areas b and d.
  • only a single ventilation channel 1C can be sufficient.
  • the venting channel 1C may each be optionally formed in the base part 1A and / or cover 1B or end.
  • the base part 1A or the bottom of the channel 3 can have favorable properties, such as a certain color or other surface properties.
  • the carrier 4 may also have recesses or other means to transport, for example, the sample 2, in particular a certain volume of the sample 2, and / or record.
  • the support 4 may itself be in the form of a microfluidic system with at least one channel, a chamber and / or a reservoir for a reagent or the like.
  • the carrier 4 can also serve to transport at least one reagent, for example the reagent 21.
  • the carrier 4 may be provided with the dried-in reagent 21, which dissolves in the desired manner when the carrier 4 is introduced into the sample 2 or another liquid and then can react, for example.
  • the carrier 4 is provided or equipped with all reagents 21, antibodies 7 and / or other substances or substances which are required for the determination or detection of a particular analyte or several specific analytes or parameters or the like.
  • a suitable carrier 4 can be inserted into the device 1 or the channel 3.
  • different carriers 4 in a channel 3 and a microfluidic system for Determination of different analytes, parameters or the same can be used.
  • the various carriers 4 can then be successively moved into the sample 2 or brought into contact therewith.
  • the detection or binding regions 5 on the carrier 4 may also be omitted, in particular if the carrier 4 is used, for example, only or substantially only for mixing or transport purposes and / or forms another reaction system or microfluidic system or the like.
  • detection or binding regions 5 are particularly preferably microstructured, as already mentioned. However, such microstructuring is only optional.
  • Immobilizing the antibodies 7 on the carrier 4 or its surface 4a or in the respective detection or binding region 5 or in different detection or binding regions 5 by prior plasma coating and / or silanization of the carrier 4, at least into the desired one, is particularly preferred areas.
  • a so-called photolinking of the antibody 7 can take place, whereby the density of the bound antibodies 7 can be substantially increased.
  • any suitable treatment is possible. This is a further advantage of the proposed device 1, the proposed carrier 4 and the proposed method.
  • Fig. 4 shows in a schematic, too Fig. 1 Corresponding plan view of a second embodiment of the proposed device 1.
  • the channel 3 here has a branch or forms a kind of switch.
  • the carrier 4 is starting from the region b or from preferably only a single gas space optionally in a plurality, in particular in at least three different areas a, c and d and / or reaction chambers movable, in particular optionally in at least three different liquids, namely the sample 2, the liquid 15 and the liquid sixteenth
  • the movement of the carrier 4 is preferably controlled again by the manipulation device 8, not shown here.
  • the device 1 or the channel 3 or the preferably microfluidic system may also have a plurality of branches or a branch with even more different channel regions or channel buttons or the like.
  • a plurality of carriers 4 in the device 1 or the channel 3 or the system can be used, which can be arranged in the desired manner depending on the number of branches, reaction chambers or the like, in particular desired processes, manipulations and / or investigations perform.
  • Fig. 5 shows a schematic section of a proposed test device 22 with the proposed device 1.
  • the test device 22 has in particular a receiving area 23 for the device 1.
  • the receiving region 23 is designed in particular as an insertion region and / or slit-like.
  • the device 1 it is also possible, for example, for the device 1 to be placed on the receiving area 23 of the test device 22 for detection or evaluation, or in any other way with the test device 22 or the receiving area 23 in preferably mechanical contact or at least in the vicinity is brought about, in particular to allow the magnetic manipulation of the carrier 4 and / or the preferably optical detection.
  • the test device 22 preferably has the detection device 17 with the measuring or sensor devices 18 for the already explained detection, in particular optical detection, particularly preferably by luminescence and / or fluorescence measurement.
  • the test device 22 preferably has the manipulation device 8 or the electromagnets, which are preferably provided for this purpose, and particularly preferably an associated controller, not shown, or the like.
  • the manipulation device 8 By means of the manipulation device 8, the carrier 4 is moved in the desired manner as already explained, in the device or in the channel 3 or microfluidic system.
  • the measured values of the detection device 17 are preferably detected, recorded, further evaluated, stored and / or further processed by an evaluation device 24 and output, for example, via an output device 25 of the test device 22.
  • the output device 25 can in particular be a display, but also an interface or the like.
  • test device 22 represents a preferably mobile device that can be used together with the device 1 as a POC system.
  • the proposed POC system of test device 22 and device 1 can accordingly be used universally.
  • the device 1 can first be filled with the sample 2 and then introduced into the receiving region 23 of the test device 22 in order to carry out the desired reaction, detection and evaluation.
  • the carrier 4 in the device 1 is preferably held securely in a predetermined area, for example the area a or the area b, until the actual use of the device 1 takes place, in particular until the sample 2 is filled.
  • the device 1 and / or the carrier 4 may be provided with a corresponding holding means.
  • the holding means may be, for example, a sticking, sticking or the like.
  • the holding means may also be formed by a mechanical or chemical compound or the like.
  • the holding means may also be realized by a positive or positive connection, for example a pinching or the like.
  • the carrier 4 may also be magnetically held at a desired position, for example by installation a permanent magnet in the device 1 and the base part 1A at a desired location.

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  • Physical Or Chemical Processes And Apparatus (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
  • Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
  • Micromachines (AREA)

Claims (15)

  1. Dispositif (1) de manipulation ou d'étude d'un échantillon liquide (2), le dispositif présentant un canal microfluide (3) qui reprend l'échantillon (2) et dans le canal (3) un support (4) mobile et présentant au moins une zone (5) de détection ou de liaison pour une substance,
    la substance étant ou contenant en particulier un analyte de l'échantillon (2), un complexe (6) forme par ce dernier, un produit de réaction qui en dépend ou un réactif qui interagit avec un analyte de l'échantillon (2) ou qui se lie à ce dernier, un complexe (6) formé par ce dernier ou un produit de réaction qui en dépend, caractérisé en ce que
    le support (4) est guidé dans une orientation définie au moyen du canal (3),
    en ce que le support (4) a la forme d'une plaque de forme stable et définie et
    en ce que le support est une pièce en matière synthétique ou une pièce moulée par injection.
  2. Dispositif selon la revendication 1, caractérisé en ce que le support (4) présente une longueur supérieure à la section transversale maximale du canal (3) et/ou en ce que le support (4) remplit plus de 30 % de la superficie de la section transversal du canal (3).
  3. Dispositif selon les revendications 1 ou 2, caractérisé en ce que le support (4) présente un côté supérieur au moins essentiellement plan doté de la zone (5) de détection ou de liaison, en ce que la zone (5) de détection ou de liaison est microstructurée et/ou en ce qu'un dispositif de manipulation (8) est prévu pour déplacer le support (4) hors de l'échantillon (2).
  4. Dispositif selon l'une des revendications précédentes, caractérisé en ce que le support (4) présente plusieurs zones différentes de détection ou de liaison (5), en particulier sur un côté plat.
  5. Dispositif selon l'une des revendications précédentes, caractérisé en ce que le support (4) peut être déplacé magnétiquement et/ou sans contact.
  6. Dispositif selon l'une des revendications précédentes, caractérisé en ce que le support (4) peut être déplacé et/ou déplacé en va-et-vient essentiellement en ligne droite dans le canal (3).
  7. Dispositif selon l'une des revendications précédentes, caractérisé en ce que le réactif est un anticorps (7) ou contient un anticorps (7).
  8. Dispositif selon l'une des revendications précédentes, caractérisé en ce que la zone de détection ou de liaison (5) est formée ou recouverte par des anticorps (7) immobilisés.
  9. Dispositif selon l'une des revendications précédentes, caractérisé en ce que le dispositif (1) forme une immunodétermination.
  10. Dispositif selon l'une des revendications précédentes, caractérisé en ce que le dispositif (1) ne présente qu'un seul support (4) ou en ce qu'un seul support mobile (4) est prévu dans le canal (3).
  11. Dispositif selon l'une des revendications précédentes, caractérisé en ce que le support (4) a une forme allongée.
  12. Dispositif selon l'une des revendications précédentes, caractérisé en ce que le canal (3) présente au moins un moyen qui permet de maintenir l'échantillon (2) dans une partie du canal (3) qui forme une chambre de réaction.
  13. Dispositif selon l'une des revendications précédentes, caractérisé en ce qu'un espace prévu pour le gaz dans le canal (3) se raccorde à une partie du canal (3) qui contient l'échantillon (2) et qui forme une chambre de réaction et en ce que le support (4) peut être éloigné au-delà d'une frontière de phase et/ou peut être déplacé dans l'espace pour le gaz ou à travers ce dernier.
  14. Dispositif selon l'une des revendications précédentes, caractérisé en ce qu'une liaison de la substance ou d'autres modifications dans la zone de détection ou de liaison (5), en particulier pour la détermination d'un analyte dans l'échantillon (2), peuvent être détectées optiquement, en particulier lorsque le support (4) se trouve dans un espace prévu pour le gaz.
  15. Dispositif selon l'une des revendications précédentes, caractérisé en ce que le support (4) peut être déplacé sélectivement dans différentes parties du canal (3), dans différentes chambres de réaction et/ou dans au moins un liquide différent de l'échantillon (2), ou inversement.
EP20100002685 2010-03-15 2010-03-15 Dispositif et procédé de manipulation ou d'analyse d'un échantillon liquide Active EP2369343B1 (fr)

Priority Applications (10)

Application Number Priority Date Filing Date Title
AT10002685T ATE542136T1 (de) 2010-03-15 2010-03-15 Vorrichtung und verfahren zur manipulation oder untersuchung einer flüssigen probe
EP20100002685 EP2369343B1 (fr) 2010-03-15 2010-03-15 Dispositif et procédé de manipulation ou d'analyse d'un échantillon liquide
US13/583,785 US8919383B2 (en) 2010-03-15 2011-03-14 Device and method for manipulating a liquid
EP11710687A EP2547449A1 (fr) 2010-03-15 2011-03-14 Dispositif et procédé permettant d'agir sur un liquide
JP2012557437A JP2013522014A (ja) 2010-03-15 2011-03-14 液体の取り扱い装置及び方法
PCT/EP2011/001242 WO2011113563A1 (fr) 2010-03-15 2011-03-14 Dispositif et procédé permettant d'agir sur un liquide
EP11711029.6A EP2548023B1 (fr) 2010-03-15 2011-03-14 Dispositif et procédé de manipulation ou d'analyse d'un échantillon liquide
JP2012557439A JP5551279B2 (ja) 2010-03-15 2011-03-14 液体検体を取り扱い又は分析する器具及び方法
PCT/EP2011/001254 WO2011113569A1 (fr) 2010-03-15 2011-03-14 Dispositif et procédé de manipulation ou d'examen d'un échantillon liquide
US13/583,788 US20130156643A1 (en) 2010-03-15 2011-03-14 Device and method for manipulating or analysing a liquid sample

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP20100002685 EP2369343B1 (fr) 2010-03-15 2010-03-15 Dispositif et procédé de manipulation ou d'analyse d'un échantillon liquide

Publications (2)

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EP2369343A1 EP2369343A1 (fr) 2011-09-28
EP2369343B1 true EP2369343B1 (fr) 2012-01-18

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EP20100002685 Active EP2369343B1 (fr) 2010-03-15 2010-03-15 Dispositif et procédé de manipulation ou d'analyse d'un échantillon liquide
EP11710687A Withdrawn EP2547449A1 (fr) 2010-03-15 2011-03-14 Dispositif et procédé permettant d'agir sur un liquide
EP11711029.6A Active EP2548023B1 (fr) 2010-03-15 2011-03-14 Dispositif et procédé de manipulation ou d'analyse d'un échantillon liquide

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EP11710687A Withdrawn EP2547449A1 (fr) 2010-03-15 2011-03-14 Dispositif et procédé permettant d'agir sur un liquide
EP11711029.6A Active EP2548023B1 (fr) 2010-03-15 2011-03-14 Dispositif et procédé de manipulation ou d'analyse d'un échantillon liquide

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US (2) US8919383B2 (fr)
EP (3) EP2369343B1 (fr)
JP (2) JP2013522014A (fr)
AT (1) ATE542136T1 (fr)
WO (2) WO2011113563A1 (fr)

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Also Published As

Publication number Publication date
WO2011113569A1 (fr) 2011-09-22
US20130206264A1 (en) 2013-08-15
US20130156643A1 (en) 2013-06-20
WO2011113563A1 (fr) 2011-09-22
JP2013522609A (ja) 2013-06-13
EP2548023B1 (fr) 2016-11-16
JP2013522014A (ja) 2013-06-13
US8919383B2 (en) 2014-12-30
EP2547449A1 (fr) 2013-01-23
EP2548023A1 (fr) 2013-01-23
EP2369343A1 (fr) 2011-09-28
ATE542136T1 (de) 2012-02-15
JP5551279B2 (ja) 2014-07-16

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